Mutations

PSEN1 P284L

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease, Spastic Paraparesis
Reference Assembly: GRCh37 (105)
Position: Chr14:73664820 C>T
dbSNP ID: rs63750863
Coding/Non-Coding: Coding
Genomic Region: Exon 8
Mutation Type: Point, Missense
Codon Change: CCA to CTA

Findings

This mutation was identified in a Japanese woman with dementia and parkinsonism (Tabira et al., 2002). Family history was unknown. Her symptoms started at age 32 with spastic paraparesis leading to falls. She later developed dysarthria (difficulty pronouncing words) and dementia. She died at age 54.

Neuropathology

Autopsy showed cortical atrophy, enlarged ventricles, and neuronal loss, especially in the hippocampus, substantia nigra, and locus coeruleus. Abundant amyloid pathology was observed, notably cotton-wool plaques in the cerebral cortex, basal ganglia, brainstem, and spinal cord. Some cored plaques were seen, mainly in the hippocampus and cerebral cortex, where neurofibrillary tangles were also observed. Neuritic changes and glial activation were mild, and prion staining was absent. Vacuolar changes were noted in the cerebral cortex, along with amyloid angiopathy in vessel walls (Tabira et al., 2002).

Biological Effect

Unknown.

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References

Paper Citations

  1. . Alzheimer's disease with spastic paresis and cotton wool type plaques. J Neurosci Res. 2002 Nov 1;70(3):367-72. PubMed.

Further Reading

Learn More

  1. Alzheimer Disease & Frontotemporal Dementia Mutation Database
  2. Japanese Familial Alzheimer's Disease Database

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Primary Papers

  1. . Alzheimer's disease with spastic paresis and cotton wool type plaques. J Neurosci Res. 2002 Nov 1;70(3):367-72. PubMed.

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